The incretin effect
The observation that started incretin science: glucose taken by mouth triggers far more insulin than the same glucose given intravenously.
Give someone glucose by mouth and their insulin response is substantially larger than if the identical amount of glucose is infused into a vein to produce the same blood concentration. The difference — historically on the order of half or more of the total insulin response to a meal — is the incretin effect. Something in the gut, not just the glucose itself, is signalling the pancreas.
That something is a pair of hormones released by the intestine in response to food: GLP-1 and GIP. Both amplify insulin secretion, and both do so in a glucose-dependent way — they enhance insulin release when glucose is elevated and much less so when it is not. That dependence is the reason incretin-based approaches carry a lower intrinsic hypoglycaemia risk than agents that force insulin release regardless of glucose.
The incretin effect is blunted in type 2 diabetes, which is what made this physiology a therapeutic target rather than a curiosity. See Metabolic syndrome for the wider context.
Related articles
- MetabolicGLP-1 receptor agonistsHow GLP-1 works, and why molecules mimicking it became central to metabolic research.
- MetabolicGIP and its receptorThe other incretin hormone — long overshadowed by GLP-1, now central to combination approaches.
- MetabolicMetabolic syndromeThe cluster of findings — central adiposity, dysglycaemia, dyslipidaemia, raised blood pressure — that tend to travel together.
- MetabolicGastric emptying and satiety signalingThe gut-brain routes through which incretin signaling reduces food intake.
- MetabolicDual GIP/GLP-1 receptor agonistsEngineering one molecule to engage two incretin receptors — and what head-to-head data showed.
- MetabolicTriple agonists: GLP-1, GIP, and glucagonAdding glucagon receptor activity to incretin agonism — using a hormone long considered the opposition.